Two current projects are related to the study of diseases associated with abnormalities in the metabolism of biogenic amines. One involves the use of the enzymatic isotopic assay of histamine to study histamine release in pathological reactions. The discovery of a new, more potent source of histamine-N-methyltransferase, the enzyme used in the assay, has made it possible, for the first time, to measure histamine levels (0.6 ng/ml, range 0.1-1.4) in normal human plasma. The other is concerned with the presence of enzymes in tumors believed to be derived from APUD cells. DOPA decarboxylase was found in medullary thyroid carcinoma, small cell carcinoma of the lung, and pheochromocytoma as well as in the cells from which these tumors are believed to arise (calcitonin "C" cell and adrenal medullary cells). Diamine oxidase was also found in high amounts in the thyroid and lung tumor. This enzyme is not a normal constituent of the C cell and appears to be an expression of the tumor cell itself. L-DOPA significantly reduced the ability of the thyroid tumor to release of calcitonin (in vivo and in vitro). Administration of DOPA decarboxylase inhibitors reversed the effects of L-DOPA and by themselves enhanced release. These findings support the suggestion that monoamines may have a regulatory role in peptide hormone release.